The FDA has granted Huida Gene Therapeutics clearance for its investigational new drug (IND) application in support of launching a multi-national trial assessing HG004 as treatment for patients with inherited retinal dystrophies (IRD) linked to RPE65 mutations.
Refresh me on HuidaGene Therapeutics.
The global, clinical-stage biotechnology company is based in Shanghai and New Jersey, and is focused on the development of clustered regularly interspaced short palindromic repeats (CRISPR)-based genetic medicine
Tell me about HG004.
HG004 is a novel ophthalmic injection designed to treat RPE65 retinopathies.
A head-to-head, preclinical study compared equal dosages of HG004 and adeno-associated virus serotype 2 (AAV2). Retinal function recovery was found to increase by 67.6% for HG004 and 35.8% for AAV2 products when assessed using an RPE65 gene knockout murine disease model.
So it performs better than AAV2?
Essentially, yes. HG004 performed better with transduction efficiency and substantial vision loss restoration at the level of the retinal pigment epithelium (RPE) comparatively to AAV2. HuidaGene stated that it shows the potential for lowering the total number of vector doses, leading to a reduced risk for ocular adverse events (AEs) in humans. (via)
So what’s the goal?
According to HuidaGene, the HG004 program is looking to create a one-time, non-AAV2 gene replacement to restore, treat, and prevent pediatric/adult blindness in patients already experiencing severe visual impairment/blindness due to RPE65-associated retinopathies. (via)
Now tell me about the upcoming trial.
The multi-national, multi-center, multiple-cohort, dose-finding study will evaluate adult and pediatric patients with RPE65 retinopathies using one master protocol. The safety, tolerability, efficacy, and long-term clinical durability of one HG004 injection is being assessed for up to 52 weeks.
Primary endpoints include adverse events, ophthalmic examinations, and certain laboratory measures.
What are patients being assessed on?
Patients’ visual function will be observed through a multiluminance mobility test (MLMT) that will require them to maneuver a mobility course via various light levels. The company plans on launching the trial within the first half of 2023.
For how long?
Following completion of the primary multinational study, participants will continue to receive evaluation through a long-term follow-up study on HG004.